Effect and Underlying Mechanism of Bu-Shen-An-Tai Recipe on Ovarian Apoptosis in Mice with Controlled Ovarian Hyperstimulation Implantation Dysfunction

The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation(COH) implantation dysfunction were studied. The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare’s serum gonadotrophin(PMSG), followed by 7.5 IU human chorionic gonadotrophin(HCG) 48 h later. Then the female mice were mated with male at a ratio of 2:1 in the same cage at 6:00 p.m. The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time. Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m. of the next day. Fifty successfully pregnant mice were equally randomly divided into 5 groups: normal control pregnant group(NC), COH implantation dysfunction model group(COH), low dosage of Bu-Shen-An-Tai recipe group(LOW), middle dosage of Bu-Shen-An-Tai recipe group(MID) and high dosage of Bu-Shen-An-Tai recipe group(HIGH). Then from day 1, the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m. for 5 consecutive days. The concentrations of 17β-estradiol(E) and progesterone(P) were determined by radioimmunoassay(RIA). The ultrastructural changes of ovarian tissues were observed by transmission electron microscope(TEM). The histopathological changes of ovarian tissues were observed by HE staining. The number of atretic follicles and pregnant corpus luteum were also recorded. TUNEL was applied to measure apoptotic cells of ovarian tissues. Western blotting was used to detect the protein expression of apoptosis-related factors like Bax, Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice. The results showed that ovarian weight, the concentrations of Eand P, the number of atretic follicles and pregnant corpus luteum, as well as the apoptosis of granulosa cells were significantly increased in the COH group. The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased, agglutinated, aggregated or crescent-shaped. The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis. After the treatment with different doses of Bu-Shen-An-Tai recipe, the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM. Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced. The lipid dropltes were shown in a circluar or oval shape. The protein expression levels of Bax and cleaved-caspase-3 were decreased, and the expression of Bcl-2 protein was increased after treatment. It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells, probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3, which contributes to the formation and maintenance of ovarian corpus luteum. It’s helpful to promote the embryonic implantation, to reduce embryo loss and ultimately to improve the success rate of pregnancy.

Endometrial Mucin-1 and Pinopode in Peri-implantation Phase in Ovarian High Responders during Controlled Ovarian Hyperstimulation Cycles

Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response was defined as serum E2 〉 15 000 pmol/L on the day of hCG administration in COH cycle using GnRH agonist and recombinant FSH （n=8）. Healthy and fertile women were used as the natural control （n=10）. Endometrial biopsies were performed on the day of LH＋ 7/hCG＋ 7. Pinopode formation was observed by scanning electron microscope. Expression of MUC1 was detected with quantitative Real-time PCR and immunohistochemistry. Results In high response group, the lumen surface was covered with variant pinopodes and microvillous. The expression of MUC1 mRNA in high response group was lower than that in the natural control （P〈0.05）. Immunostaining for MUC1 protein in glandular and luminal epithelium in high response group was lower than that in the natural control （P〈0. 05）. Conclusion Asynchronized pinopode appearance and lower expression of MUC1 during peri-implantation period were the characteristics of endometrium in high response group, Which may provide a clue of decreased endometrial receptivity in the supraphysiological hormone milieu.

Missed estradiol determination resulting in oocyte retrieval and embryo development following controlled ovarian hyperstimulation at early pregnancy: Case report

This paper is a case report on the success of oocyte retrieval and good quality embryo development following controlled ovarian hyperstimulation at early pregnancy. A 30-year-old patient underwent controlled ovarian hyperstimulation by gonadotropin-releasing hormone agonist long protocol. On the day of oocyte collection, a 5-week gestational sac was observed by exact sonography monitoring. However, via ultrasound guided follicle puncture, 7 oocytes were collected. After intarcytoplasmic sperm injection, 3 developed good quality embryos were cryopreserved. Moreover, the natural pregnancy was continued and finally a healthy live birth was achieved. Despite physiological hormonal changes during pregnancy, the follicular growth occurred and followed by oocyte retrieval and embryo development, subsequently.

Pharmacotherapy Cost of Controlled Ovarian Hyperstimulation of <i>in Vitro</i>Fertilization—A Real Life Study

The aim of the current study is to analyze the cost of controlled ovarian hyperstimulation (COH) of in vitro fertilization (IVF) during the period 2009-2013 in a specialized gynecology clinic. It is a prospective, observational study and bottom up cost analysis of the COH pharmacotherapy of IVF. The data was collected for all women admitted to the clinic, therapeutic COH protocols, prescribed medicines and doses, average length of therapy and its cost. Statistical analysis is applied towards the pharmacotherapy and cost data. On average 136 (SD 21.92) women were admitted varying from 105 to 179 for 10.7 (SD 1.47) days. 11% were on long (GnRH agonist containing) therapeutic COH protocol and all other on short (GnRH antagonist containing). Therapeutic protocols include Follitropin-α IU (103 women at average dose of 1171 IU (SD 314.16));Follitropin-β IU (299 women at average dose of 1634 IU (SD 423.5));Urofollitropin 75 IU amp (243 women at average dose of 21.3 IU (SD 7.37));urFSH + urLH 75IU:75IU/amp (354 women at average dose of 23.4 IU (SD 8.8));cetrorelix amp 0.25 mg prescribed at 264 women at average dose of 3.84 IU (SD 1.32);ganirelix amp 0.25 mg for 299 women at average dose of 4.01 mg (SD 1.32);Human chorion gonadotropin for 535 women at average dose of 6752.52 IU (SD 1216.23);Nafarelin mcg/ml for 8 women at dose of 17,700 mcg (SD 10,725);triptorelinacetat 0.1 mg amp - 63 women at doses of 5.5 (SD 3.25) mg at 14 women and average dose of 7.5 mg (SD 2.5);clomiphen citrate and letrozole for 15 women at average dose of 8 mg (SD 2.4). The average cost of COH pharmacotherapy is varying among the years with highest value of 1803.776 (SD - 624.89) BGN in 2009. Controlled ovarian hyperstimulation of in vitro fertilization is cost and resource consuming procedure in regards to pharmacotherapy. Age and reason of infertility influence significantly the cost.

Case Report of Ectopic Pregnancy during Controlled Ovarian Stimulation without Oocytes Harvested and Late Ovarian Hyperstimulation Syndrome

Here we reported a rare case of misdiagnosed ectopic pregnancy (EP) due to unintended ovulation during controlled ovarian stimulation (COS) in GnRH agonist cycle, resulting in no oocytes harvested and late hyper-stimulation syndrome (OHSS). The patient was a 33-year old primary infertile woman due to male’s factors and underwent her second in vitro fertilization (IVF) cycle using GnRH agonist protocol, and no oocytes harvested on ovum picked-up (OPU) day. The start of gonadotropin usage was on day 8th of her period, and the P level increased rapidly and strangely high from day 8th after gonadotropin usage. The E2 level and follicles grew normally but finally no oocytes harvested. She was diagnosed as late ovarian hyper-stimulation syndrome (OHSS) 7 days after OPU. 20 days after OPU, no menstruation come and a positive urine test of hCG were reported. And the patient was diagnosed as EP by laparoscopy. In conclusion, rapidly increased P level, no oocyte retrieval and late onset of OHSS should be very important clues to diagnose this misdiagnosed EP.

Treatment of Unexplained Infertility by Acupuncture in Natural and Control Ovarian Hyperstimulation Cycles: A Prospective Analysis

Acupuncture is an important method of treatment in Chinese medicine. The objective of this study was to evaluate the efficacy of acupuncture as an adjuvant treatment for unexplained infertility. Here we conducted a prospective study, with data consisting of acupuncture group (38 cases) and control group (42 cases). Infertility evaluation workup consisted of semen analysis, ovulation assessment, hysterosalpingogram (HSG) and blood analysis. The patients in acupuncture group received 3 acupuncture sessions, and each at seven acupuncture points (EX-CA1, CV4, CV6, SP10, ST36, SP6, and KI3). The session started 12 days before menstruation and continued for 10 days. The patients in control group did not receive acupuncture. All patients tried 1 - 3 natural cycles 3 months after HSG test, if not pregnant, underwent 1 - 3 cycles of control ovarian hyperstimulation (COH) and timed intercourse. Pregnancy was evaluated by measurement of blood β human chorionic gonadotrophin (β-hCG) and subsequent trans-vaginal ultrasound. No significant difference of clinical pregnancy rate was found between the acupuncture group and the control group, however, numbers of COH cycles were significantly less and more pregnancies occurred in natural cycle in the acupuncture group. We concluded that acupuncture can be used as an adjuvant treatment for unexplained infertility. Although acupuncture did not increase the cumulative pregnancy rate, it decreased the number of COH cycles and more patients got pregnant in natural cycles after receiving acupuncture.

Flexible GnRH Antagonist Protocol versus Progestin-primed Ovarian Stimulation (PPOS) Protocol in Patients with Polycystic Ovary Syndrome: Comparison of Clinical Outcomes and Ovarian Response

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.

Anti-Müllerian hormone and antral follicle count predict ovarian response in women less than 45 years following GnRH antagonist multiple-dose protocol

Objective:To speculate which of the following parameters:antral follicle count(AFC),anti-Müllerian hormone(AMH),follicle-stimulating hormone(FSH)and age can be used as a predictor of ovarian response to gonadotropin-releasing hormone(GnRH)antagonist stimulation multiple-dose protocol in women under 45 years,and to determine the cutoff value of these parameters and their correlations for predicting low and high ovarian response.Methods:This prospective study included 462 women with the mean age of(29.3±6.5)years.All women were subjected to the GnRH antagonist stimulation multiple-dose protocol.On the second day of the menstrual cycle,ultrasonography was conducted to determine AFC in both ovaries.Peripheral blood samples were collected to evaluate the level of estradiol,FSH,luteinizing hormone,prolactin,thyroid-stimulating hormone,and AMH.The women were divided into three groups:low response(AHH<1 ng/mL,n=173),normal response(AMH=1.0-3.5 ng/mL,n=175),and high response(AMH>3.5 ng/mL,n=114).Results:A significant decrease was found in the age and FSH level in the high response group compared to other groups(P<0.001).Conversely,a significant increase was shown in AMH,estradiol on human chorionic gonadotropin(hCG)day,AFC,mature oocytes,fertilized oocytes,and embryos transferred in the high response group compared to the other two groups(P<0.001).The receiver operating characteristic(ROC)curves demonstrated that AFC and AMH had the highest accuracy,followed by basal FSH level and age in the prediction of low ovarian reserves(P<0.001)with cutoff values of≤4.50 and≤0.95 for AFC and AMH,respectively.Moreover,the ROC analysis showed that AFC had the highest accuracy,followed by AMH level and age in the prediction of high ovarian reserves with a cutoff value of≥14.50,≥3.63,and≤27.50 years,respectively(P<0.01).A significant decrease was observed in women's age,estradiol level,and oocyte fertilization rate in pregnant women compared to non-pregnant women(P<0.001).Additionally,significant negative correlations were found between the AFC,the number of mature oocytes,fertilized oocytes,embryos transferred,and the age of pregnant women(P<0.001).Conclusions:AFC and AMH predict low and high ovarian response to GnRH antagonist stimulation multiple-dose protocol in women under 45 years.

黄体期长方案与拮抗剂方案在首次拮抗剂失败后PCOS患者中的应用比较

目的探讨首次拮抗剂治疗失败的多囊卵巢综合征(PCOS)患者再次超促排卵时分别采用黄体期长方案和拮抗剂方案诱导排卵的临床效果及妊娠结局的优劣。方法检索首次采用拮抗剂方案行IVF/ICSI-ET助孕失败后再次超促排卵的PCOS患者163例,根据第二次超促排卵方案,分为黄体期长方案组(共95例)和拮抗剂方案组(共68例)。回顾性分析比较两组患者的基础临床资料、临床及实验室指标及妊娠结局。结果①两组患者的基础临床指标除了LH,其他指标差异均无统计学意义。②黄体期长方案组患者自身超排卵对比,促性腺激素(Gn)启动剂量、Gn总天数、Gn总使用量、hCG注射日雌二醇(E_(2))值、获卵数、卵子成熟率、2PN受精数、2PN卵裂数、囊胚形成率、优质囊胚形成率显著高于首次拮抗剂周期(P<0.05)。拮抗剂方案组患者自身超排卵对比也观察到类似改善。③两组第二次超促排卵周期比较,黄体期长方案组Gn总天数、总用量、总费用较高(P<0.05),而hCG注射日E_(2)及LH水平、卵子成熟率显著低于拮抗剂方案(P<0.05),但两组间获卵数、2PN受精数、2PN卵裂数、囊胚形成率、OHSS率差异无统计学意义。④两组第二次超促排卵新鲜移植周期比较,黄体期长方案新鲜移植率、种植率、临床妊娠率及活产率略高,但差异无统计学意义。首次解冻周期的妊娠结局比较,拮抗剂组的生化妊娠率、临床妊娠率高于黄体期长方案组(P<0.05),但着床率、活产率、新生儿胎龄及出生体质量差异无统计学意义。结论对于首次拮抗剂方案治疗失败的患者,适当增加Gn启动剂量及用量,两种方案均能获得满意的妊娠结局。相较于黄体期长方案,再次使用拮抗剂方案保持了其优势,包括治疗周期短、成本低、患者依从性好。

GnRH拮抗剂和激动剂方案中扳机日子宫内膜厚度对新鲜移植周期妊娠结局的影响

目的:研究促性腺激素释放激素拮抗剂(GnRH-ant)和激动剂(GnRH-a)方案中扳机日子宫内膜厚度(EMT)对新鲜移植周期妊娠结局的影响。方法:选择2015年1月至2021年12月在郑州大学第二附属医院生殖中心接受体外受精/卵胞浆内单精子显微注射(IVF/ICSI)助孕的患者,共纳入新鲜移植2 559周期,其中GnRH-ant方案298周期,GnRH-a方案2 261周期。根据扳机日EMT分为7~9 mm、>9~12 mm和>12 mm组。比较两种方案中3组的临床特征和妊娠结局。结果:GnRH-ant方案中EMT 7~9 mm组的临床妊娠率、持续妊娠率和活产率均低于其他两组(P<0.017);GnRH-a方案中扳机日EMT 7~9 mm组的临床妊娠率、持续妊娠率和活产率低于>9~12 mm组,>9~12 mm组低于>12 mm组(P<0.017)。Logistic回归分析结果显示扳机日EMT较高的患者临床妊娠、持续妊娠和活产增加[GnRH-ant方案:>9~12 mm组的OR(95%CI)分别为2.243(1.173~4.288)、3.995(1.891~8.438)、3.814(1.810~8.036),>12 mm组的OR(95%CI)分别为3.298(1.490~7.299)、6.637(2.742~16.065)、5.249(2.184~12.616);GnRH-a方案:>9~12 mm组的OR(95%CI)分别为1.561(1.266~1.925)、1.378(1.112~1.707)、1.448(1.166~1.798),>12 mm组的OR(95%CI)分别为2.266(1.747~2.940)、2.257(1.736~2.933)、2.254(1.732~2.933)]。结论:扳机日EMT增加可改善妊娠结局;无论是GnRH-ant方案,还是GnRH-a方案,随着扳机日EMT增加,妊娠成功率升高。

控制性超促排卵对子宫内膜的影响

控制性超促排卵(controlled ovarian hyperstimulation,COH)是辅助生殖技术的重要组成部分,可显著提高体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)的妊娠率。尽管COH在促进卵泡发育和获取卵母细胞数量方面可获得明显的益处,并能够选择高质量的胚胎进行移植,但COH可能涉及种植窗、子宫内膜容受性、孕酮和雌二醇以及子宫收缩功能的改变,影响不孕患者的胚胎种植率和IVF妊娠率。本文就COH后子宫内膜变化的病理生理机制进行综述,以更好地解决不孕症临床治疗的瓶颈问题。

经后增殖方对控制性超促排卵大鼠卵巢GDF9分泌及颗粒细胞凋亡的影响

目的观察益气血法经后增殖方通过p38MAPK/CK2/IκBα/NF-κB通路对控制性超促排卵(COH)大鼠卵巢GDF9分泌及颗粒细胞(GCs)凋亡的影响。方法建立COH大鼠模型,18只大鼠随机分为自然排卵组(NO组)、COH组、COH+经后增殖方组(COH+JHZZG组)。qRT-PCR和Western blot法检测p38MAPK、CK2、IκBα、NF-κB、GDF9 mRNA和蛋白的表达水平,TUNEL法检测卵巢GCs凋亡率。结果与NO组比较,COH组大鼠卵巢组织p38MAPK、NF-κB表达升高,CK2、IκBα、GDF9表达下降,卵巢GCs凋亡率升高,差异有统计学意义(P<0.01);与COH组比较,COH+JHZZG组大鼠卵巢组织p38MAPK、NF-κB表达下降,CK2、IκBα、GDF9表达升高,差异有统计学意义(P<0.01);卵巢GCs凋亡率下降,差异有统计学意义(P<0.05)。结论益气血法经后增殖方通过p38MAPK/CK2/IκBα/NF-κB通路促进COH大鼠卵巢GDF9的分泌,抑制卵巢GCs的凋亡,从而提高COH卵细胞质量。

波塞冬1组患者重复周期应用早卵泡期长效长方案和拮抗剂方案的疗效比较及自身对照研究

目的探讨早卵泡期长效长方案和拮抗剂方案在波塞冬1组患者重复周期中的应用疗效及优化策略。方法选择2018年6月至2022年6月于安徽省妇幼保健院生殖中心行体外受精(IVF)/卵胞浆内单精子注射(ICSI)治疗、采用常规控制性促排卵(COH)方案发生非预期卵巢低反应(uPOR)、且助孕失败后再次助孕的波塞冬1组患者286例为研究对象,根据重复周期COH方案不同分为早卵泡期长效长方案组(简称早长方案组,n=119例)和拮抗剂方案组(n=167例),比较两组实验室指标及临床妊娠结局;并将其中前后两个周期均采用相同COH方案的124例患者分为双早长方案组(n=70例)和双拮抗剂方案组(n=54例),采用自身对照研究分析两组临床资料。结果(1)再次COH周期早长方案组与拮抗剂方案组患者间基础资料比较无统计学差异(P>0.05)。早长方案组促性腺激素(Gn)总量、Gn天数、HCG日E_(2)水平、获卵数、可用胚胎数及优质胚胎数均显著高于拮抗剂方案组(P<0.05),HCG日LH水平显著低于拮抗剂方案组(P<0.05),其鲜胚种植率、鲜胚临床妊娠率及累积妊娠率较拮抗剂方案组有升高趋势,但无统计学差异(P>0.05);两组患者间周期取消率、中重度卵巢过度刺激综合征(OHSS)发生率、HCG日孕酮(P)水平、HCG日内膜厚度、再次uPOR发生率及早期流产率等比较均无统计学差异(P>0.05)。(2)双早长方案组的自身对照比较结果显示,再次早长方案组Gn启动剂量、LH添加量、HCG日E_(2)水平、获卵数、可用胚胎数、优质胚胎数、正常受精率、优质胚胎率、鲜胚种植率和临床妊娠率均显著高于首次早长方案组(P<0.05),早期流产率显著低于首次早长方案组(P<0.05)。(3)双拮抗剂方案组的自身对照比较结果显示,再次拮抗剂方案组Gn启动剂量、LH添加量、获卵数、可用胚胎数、优质胚胎数、鲜胚种植率及临床妊娠率等均显著高于首次拮抗剂方案组(P<0.05)。结论对于波塞冬1组患者来说,早卵泡期长效长方案和拮抗剂方案均可作为重复周期的促排卵方案;从获卵数及鲜胚临床妊娠结局考虑,早卵泡期长效长方案优于拮抗剂方案;从经济成本考虑,拮抗剂方案优于早卵泡期长效长方案。重复周期可根据两个方案的劣势采取优化措施来改善患者对于促排卵方案的反应性及卵母细胞质量和数量等问题,从而改善IVF/ICSI预后。

补充褪黑素的人卵母细胞体外培养成熟技术在COH周期中的应用

目的比较同一控制性超促排卵(COH)治疗周期中,体内成熟与改良技术体外培养成熟(IVM)的卵母细胞的早期胚胎发育能力及临床结局,探讨补充褪黑素的IVM技术在临床中的应用。方法收集159例患者在COH周期中的920个成熟卵母细胞进行常规体外受精(IVF/ICSI)处理,同时收集同周期中1283个未成熟卵母细胞,在添加褪黑素的改良IVM培养基中培养成熟后行ICSI处理。通过回顾性分析,比较常规助孕技术与改良IVM技术这两种方式,对辅助生殖治疗的助孕结局和妊娠结局的影响。结果与从COH周期中收集到的行常规IVF/ICSI处理的成熟卵母细胞相比,经改良IVM技术促成熟的卵母细胞的优质囊胚形成率较低。但经胚胎移植后,两种方式获得的成熟卵母细胞的临床结局包括临床妊娠率、足月产率、婴儿体长、新生儿Apgar评分,差异均无统计学意义。结论IVM可以提高从COH周期中回收的未成熟卵母细胞的卵子利用率,改善辅助生殖技术助孕患者的妊娠结局。

Efficacy and safety of Yiqi Huoxue Jiedu decoction for the treatment of advanced epithelial ovarian cancer patients: a double-blind randomized controlled clinical trial

OBJECTIVE:To further evaluate the complementary effect of Yiqi Huoxue Jiedu decoction(YHJD)on patients with advanced epithelial ovarian cancer(EOC).METHODS:All 330 enrolled participants diagnosed with stageⅢc EOC were randomly divided into two groups that received YHJD or a placebo.The primary end point was health-related quality of life(HRQL)measured by the functional assessment of cancer therapy-ovary cancer(FACT-O)questionnaire.The secondary end point was progression-free survival(PFS).RESULTS:A total of 299 participants completed the trial with 153 and 146 in YHJD and control groups,respectively.After 6 months of treatment,YHJD increased physical wellbeing(PWB),functional wellbeing(FWB),additional concerns(AC),and the trial outcome index(TOI)(P<0.05)by various degrees compared with the baseline.YHJD also had notable advantages over the placebo at 3 and 6 months in terms of PWB,FWB,AC(P<0.05),and TOI(P<0.01).In addition,YHJD had a significant advantage in terms of PFS compared with the placebo(21 vs18 months,P<0.05).No adverse events were reported.CONCLUSION:YHJD is an effective and safe choice as a complementary therapy to improve HRQL and prolong PFS of stageⅢc EOC patients.

两种重组人卵泡刺激素注射液在不同人群中的促排卵效果分析

目的探究具有不同糖修饰谱的两种重组人卵泡刺激素(rFSH)在不同人群中行控制性促排卵(COH)临床应用的有效性和安全性。方法回顾性分析2022年1—12月期间本中心的320个COH周期的临床资料,按照COH中使用的rFSH种类不同分为A组(芳乐舒,95个周期)和B组(Puregon,225个周期)。比较两组患者在起始剂量、刺激时间、HCG日激素水平和内膜厚度、获卵数、减数分裂Ⅱ期(MⅡ)卵率、受精率、卵裂率、有效胚胎率、卵母细胞利用率和胚胎利用率等方面的差异。结果在A、B两组患者的年龄[(34.9±4.9)岁vs.(33.3±4.5)岁,P=0.006]、体质量指数(BMI)[(22.5±3.2)kg/m^(2) vs.(21.6±2.6)kg/m^(2),P=0.027]存在一定差异的前提下,A组获卵数与B组相当[(11.2±7.0)vs.(12.9±7.3),P=0.059]。在拮抗剂方案COH周期,两组患者年龄相近(P>0.05),此时两组的获卵数[(13.7±7.1)vs.(14.8±7.6),P=0.340]及其他结局指标均无统计学差异(P>0.05)。将所有患者根据年龄分层分析,高龄(≥35岁)亚组中,A组患者受精率[(78.1±19.6)%vs.(69.1±25.8)%,P=0.039]、卵裂率[(98.9±3.2)%vs.(93.7±22.1)%,P=0.039]和卵母细胞利用率[(44.9±30.6)%vs.(34.1±23.5)%,P=0.037]显著高于B组;低龄(<35岁)亚组中,A、B两组患者各项结局指标均无统计学差异(P>0.05)。通过逐步多元回归分析,确定COH方案和年龄是获卵数的预测因素(P<0.001),最终回归模型可解释28.8%的反应变异性。结论芳乐舒与Puregon两种rFSH具有相似的获卵数和获胚结局,在高龄人群中芳乐舒诱导的卵母细胞质量可能较高。

Heyan Kuntai capsule versus dehydroepiandrosterone in treating Chinese patients with infertility caused by diminished ovarian reserve： a multicenter, randomized controlled trial

OBJECTIVE: To evaluate the clinical efficacy and safety of Heyan Kuntai capsule(HYKT) in treating women with infertility caused by diminished ovarian reserve(DOR).METHODS: One hundred eight eligible patientsfrom three Chinese hospitals were randomly divided into an HYKT treatment group(n = 55) or a dehydroepiandrosterone(DHEA) treatment group(n =53). Patients in the HYKT group were treated orally with four 0.5 g HYKT three times a day; patients in the DHEA group were treated with one 25.0 mg DHEA capsule three times a day. All patients were treated for 3 months and followed up over a3-month period.RESULTS: Of 108 patients, 12 dropped out: six from the HYKT group, and six from the DHEA group. Eleven patients got pregnant during the treatment. Serum anti-Müllerian hormone levels and antral follicle counts increased significantly in both groups after treatment(P < 0.05) especially in the HYKT group(P < 0.05). Serum follicle stimulating hormone(FSH) levels and FSH/luteinizing hormone ratios decreased(P < 0.05) with no significant difference between the two groups. Estradiol levels in the HYKT group and DHEA-sulfate levels in the DHEA group both increased(P < 0.05). The spontaneous pregnancy rates were 12% and 11% in the HYKT and DHEA groups, respectively(not significant). During the follow-up period, 16 patients in the HYKT group underwent in vitro fertilization-embryo transfer(IVF-ET) and the number of retrieved oocytes was(5.1 ± 1.8). In DHEA group, 20 patients underwent IVF-ET and the number of retrieved oocyte was(4.2 ± 1.9)(not significant); clinical pregnancy rates were 38% in the HYKT group and 20%in DHEA group(not significant). No significant adverse reactions were observed.CONCLUSION: HYKT can improve the ovarian re-serve and hormone levels in patients with infertility caused by DOR. Pregnancy rates after HYKT treatment were similar to those of DHEA treatment.HYKT might be an alternative to the treatment of infertility caused by DOR.

Effects of Bushen Yiqi Huoxue Decoction in Treatment of Patients with Diminished Ovarian Reserve:A Randomized Controlled Trial

Objective:To explore the therapeutic effect of Bushen Yiqi Huoxue Decoction BYHD)in patients with diminished ovarian reserve(DOR).Methods:A total of 180 patients with DOR diagnosed from December2013 to December 2014 were equally assigned into progynova and duphaston(E+D)group,Zuogui Pill group and BYHD group with 60 cases in each by computerized randomization.Patients received E+D,Zuogui Pill or BYHD for 12 months,respectively.Follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E_(2)),anti-Mullerian hormone(AMH),antral follicle count(AFC),ovarian volume,endometrial thickness,and the resistance indices(Rls)of ovarian arteries and uterine arteries were observed before and after treatment.Results:Nine women(4 from the E+D group,3 from the Zuogui Pill group,and 2 from the BYHD group)withdrew from the study.After 6 months,Zuogui Pill and BYHD significantly decreased FSH and LH and increased endometrial thickness and AMH(all P<0.01),BYHD also resulted in E2 elevation(P<0.05),ovary enlargement(P<0.05),AFC increase(P<0.01),and RI of ovarian arteries decrease(P<0.05).After 12 months,further improvements were observed in the Zuogui Pill and BYHD groups(all P<0.01),but BYHD showed better outcomes,with lower FSH,larger ovaries and a thicker endometrium compared with the Zuogui Pill group(all P<0.01).However,E+D only significantly increased endometrial thickness(P<0.01)and no significant improvements were observed in the RI of uterine arteries in the three groups.Conclusions:BYHD had a favorable therapeutic effect in patients with DOR by rebalancing hormone levels,promoting ovulation,and repairing the thin endometrium.The combination of tonifying Shen(Kidney),benefiting qi and activating blood circulation may be a promising therapeutic strategy for DOR.

Effectiveness of tonifying-kidney and regulating-liver therapy on diminished ovarian reserve: a systematic review and Meta-analysis of randomized controlled trials

OBJECTIVE: To evaluate the effectiveness of the Traditional Chinese Medicine tonifying-kidney and regulating-liver therapy on diminished ovarian reserve(DOR).METHODS: The literature was comprehensively searched up to August 2019 using four Chinese and three English electronic databases to extract randomized clinical trials(RCTs) comparing Traditional Chinese Medicine tonifying-kidney and regulating-liver prescriptions(combined with hormone therapy or not) with Western Medicine. Data quality evaluation was conducted using the Cochrane risk of bias tool. Meta-analysis was conducted using Revman 5.3 software with effect estimates presented as mean difference(MD), risk ratio(RR), and95% confidence interval(CI).RESULTS: A total of nine RCTs with 512 participants were extracted and eligible for Meta-analysis.There were no significant differences between Chinese medicine and Western Medicine on basal serum follicle-stimulating hormone(FSH) level(MD0.11, 95% CI-0.52 to 0.74, 392 participants, seven trials), anti-Müllerian hormone level(MD 0.48, 95%CI-0.62 to 1.58, 95 participants, two trials), and the FSH and luteinizing hormone ratio(MD 0.01,95% CI-0.95 to 0.96, 115 participants, two trials).Chinese medicine was more effective at improving Traditional Chinese Medicine symptom scores(TCMSS)(MD-2.39, 95% CI-3.83 to-0.94, 160 participants, three trials), effective rate of TCMSS(RR1.18, 95% CI 1.02 to 1.36, 160 participants, three trials), antral follicle count(AFC)(MD 0.55, 95% CI 0.05 to 1.04, 155 participants, three trials), and FSH levels at 3 months post-treatment(MD-4.77, 95% CI-6.09 to-3.45, 137 participants, two trials).CONCLUSION: Compared with Western Medicine,tonifying-kidney and regulating-liver therapy is more effective at relieving symptoms and improving AFC and FSH at 3 months post-treatment.

Yiqixue Buganshen Recipe(益气血补肝肾方) Regulates the Expression of Integrin ανβ 3 in the Endometrium of Controlled Ovarian Hyperstimulation Mice

Objective： To observe the effect of Yiqixue Buganshen recipe （益气血补肝肾方, YBR） on the expression of integrin e~ v 13 3 in the endometrium of controlled ovarian hyperstimulation mice. Methods： A total of 180 mice were divided into three groups： model group, treatment group and control group. The treatment and model groups were intraperitoneally injected with gonadotropin-releasing hormone analogue for 7 days; pregnant mare serum gonadotropin was also injected on the 7th day. After 48 h, human chorionic gonadotropin was injected. The control group was injected with an equal volume of saline at the same time. From the start of the experiment, the treatment group was intragastrically administered Jinghouzengzhi Recipe （经后增殖方） and Cuhuangti Recipe （促黄体方）. The model group and the control group were intragastrically administered an equal volume of saline. Real-time reverse transcription polymerase chain reaction and Western blotting were used to detect the mRNA and protein expression of integrin α υ β 3 in mouse endometrium. Results： Integrin α υ β 3 was expressed in mouse endometrium in all groups. Integrin α υ β 3 expression increased gradually along with pregnancy, progressing from pregnant day （Pd） 1. Integrin α υ β 3 expression significantly increased on Pd 4, then began to decrease on Pd 6. Integrin α υ β 3 expression in the treatment group was higher than in the model group, and the difference was statistically significant （P〈0.05）. The difference between the treatment group and the control group was not statistically significant （P〉0.05）. Conclusion： YBR improves endometrial receptivity, and may play an important role in embryonic implantation.